Bacteriophages

Professor Benoit Coulombe

Director, Translational Proteomics Research Unit, IRCM

Professor, Department of Biochemistry and Molecular Medicine, U Montréal

Person in charge of Responsible Conduct of Research (RCR), IRCM

Interception Medicine based on Proteome Profiling and Reprogramming

Towards an Interception Medicine Clinic

I lead a remarkable research team that develops "interception medicine", a new approach that aims for the ultra-early detection and correction of molecular disturbances in cells when the phenotypic trajectory shift towards disease conditions. Since proteins are the functional actors of our cells, their role in diseases is direct and their profiling is very informative.

With Dr. Geneviève Bernard (McGill University Health Centre, MUHC) and a few other colleagues, and thanks to sustained funding from the Canadian Institutes of Health Research and the Leukodystrophy Foundation (Quebec), we discovered that, for example, genetic variations affecting subunits of RNA polymerase III, an enzyme central to the gene expression process, disrupt the assembly of this enzyme and cause ​a brain white matter disorder called leukodystrophy.

We have also found that certain defects in RNA polymerase III assembly can be at least partially reversed by treating cells with Riluzole, a compound already approved by the US FDA for amyotrophic lateral sclerosis (ALS). The effect of Riluzole in organisms with leukodystrophy-related disorders and its mechanism of action are currently being investigated in our laboratory. Aiming for the cause of the disease as a therapeutic target, i.e. the assembly of RNA polymerase III in this case, rather than its consequence, i.e. the defect in myelination that occurs months or years later, appears as a promising strategy to discover cures.

We also believe that massive profiling of the proteome of thousands of cells from patients or derived model systems at single-cell resolution will allow to more accurately follow the phenotypic trajectory of diseased cells and to better understand, diagnose and treat diseases.